MRI and PET-CT in the Diagnosis and Follow-Up of a Lymphoma Case with Multifocal Peripheral Nerve Involvement

Diagn Interv Radiol 2013; 19:25–28 MUSCULOSKELETAL IMAGING © Turkish Society of Radiology 2013 CASE REPORT

MRI and PET-CT in the diagnosis and follow-up of a lymphoma case with multifocal peripheral nerve involvement

Sachin Agrawal, Ming Tye Gi, Siok Bian Ng, Mark Edward Puhaindran, Poonam Singhania

ABSTRACT eripheral nerve lymphomas—both primary as well as those with Lymphoma of the peripheral nerve, particularly of the T-cell known systemic involvement—are extremely rare (1, 2). The liter- variety, is an extremely rare subtype of extra nodal lymphoma ature regarding peripheral nerve lymphoma is deficient, with most that has a variable response to current therapeutic regimens. P consisting of case reports (1, 3, 4). Peripheral nerve lymphoma can pres- Here, we present a patient with natural killer (NK)/T-cell lymphoma in remission who presented with a two-month history ent as diffuse or nodular nerve thickening, or as a mass, with this latter of right forearm swelling and paresthesia in the ulnar nerve variety of involvement being very rare. Here, we report a patient with distribution. Magnetic resonance imaging (MRI) showed an right ulnar nerve involvement of extranodal nasal-type natural killer ulnar nerve mass identified as a nerve sheath tumor. Frozen section and postresection biopsies showed an Epstein-Barr (NK)/T-cell lymphoma. The role of magnetic resonance imaging (MRI) virus-positive NK/T-cell lymphoma, nasal type. Consequently, and positron emission tomography-computed tomography (PET-CT) in the patient received chemotherapy following resection. Four the diagnosis and follow-up is discussed. months later, the patient developed a proximal leg mass, which was diagnosed as tibial nerve lymphoma. The patient was then treated with chemotherapy and follow-up was Case report done by positron emission tomography-computed tomogra- A 57-year-old woman with a 13-month history of NK/T-cell lympho- phy (PET-CT). In conclusion, lymphoma should be considered in the differential diagnosis of a peripheral nerve mass. ma was treated with SMILE (dexamethasone, methotrexate, ifosfamide, MRI is a useful imaging tool together with PET-CT, which l-asparaginase, and etoposide) therapy and was in remission. In April plays a beneficial role in the follow-up of these patients on 2011, she presented with right ulnar forearm swelling that had persisted therapy as well as diagnosis of new lesions. for two months and paresthesia over the ulnar 1.5 fingers. On examination, palpable swelling was noted over the mid-ulnar aspect of the right forearm. Wasting of the medial right forearm and numbness over the ulnar dermatome were observed. The remaining findings of general examination were unremarkable. Nerve conduction study showed right ulnar neuropathy with conduction block and slow- ing in the right forearm segment. MRI of the right forearm demonstrated an oval-shaped, longitudinal- ly oriented mass along the course of the ulnar nerve (Fig. 1a–e). The mass was eccentrically located along the nerve, which was shown to enter into the upper part of the mass. The mass was hypointense on T1-weighted images and hyperintense on T2-weighted and short tau in- version recovery (STIR) images. The morphology as well as magnetic resonance (MR) signal characteristics mimicked those of a neurogenic tumor. Post-gadolinium (contrast-enhanced) images showed predominantly peripheral enhancement. Most of the neurogenic tumors showed bright enhancement; predominantly peripheral enhancement was observed in cystic neurogenic tumors. The eccentric location of the mass and MR signal characteristics prompted an imaging diagnosis of cystic schwannoma (nerve sheath tumor). From the Departments of Diagnostic Imaging (S.A.  sachina- Due to the progressive neurological deficit, the patient underwent [email protected], M.T.G.), Pathology (S.B.N.), and Hand and surgery to remove the mass. Intraoperatively, the mass was seen to be Surgery (M.E.P.), National University Hospital, Singapore, Singa- attached to the nerve, and epineural dissection was performed to free pore; the Department of Radiology (P.S.), Jurong General Hospital, Singapore, Singapore. the mass from the nerve. Microscopic examination of the forearm mass showed sheets of mo- Received 10 April 2012; revision requested 8 May 2012; revision received 20 May 2012; accepted 22 May 2012. notonous medium- to large-sized lymphoid cells with markedly irregular nuclear membranes and distinct nucleoli. Some areas had a “starry-sky” Published online 13 December 2012 DOI 10.4261/1305-3825.DIR.5876-12.1 appearance with scattered macrophages containing karyorrhectic debris

25 (Fig. 1f). Mitotic figures were frequent- involvement. The mass probably in- ity in the posterior medial aspect of ly observed, and large areas of tumor volved the neurovascular bundle. The the right elbow also showed a marked necrosis were present. No obvious an- location of the mass suggested that it decrease (current SUVmax, 2.4; previous giocentric growth pattern was noted. likely involved the tibial nerve. SUVmax, 13.4), suggesting a positive Immunohistochemistry and in situ The PET-CT study (Fig. 2a–c) also response. No other/new suspicious hybridization were also performed. showed focal FDG-avid areas with adja- FDG-avid lesion was noted. The neoplastic lymphoid cells showed cent fat stranding in the posterior me- The patient is currently well with no positive staining for CD3, CD56, gran- dial aspect of the right elbow (SUVmax, signs or symptoms of disease, i.e., she zyme B, and EBER in situ hybridiza- 13.4). This finding was thought to be has achieved complete remission at the tion. The cells were negative for CD4, related to the recent surgical excision time of the writing of this manuscript. CD8, and CD20. Ki-67 showed a high of the ulnar nerve lymphoma; how- proliferative index of more than 90%. ever, the possibility of an underlying Discussion The phenotype was consistent with a residual tumor was not excluded. No Lymphomatous involvement of a pe- diagnosis of Epstein-Barr virus-positive suspicious FDG-avid nodal or visceral ripheral nerve presenting as a solitary extranodal NK/T-cell lymphoma, nasal disease was observed elsewhere. fusiform mass is extremely rare (1, 2). type. The patient received chemotherapy, Most such cases present as diffuse or Bone marrow biopsy showed no ev- and a follow-up PET-CT study (Fig. 3) solitary thickening of the nerves/nerve idence of tumor. However, in late July was performed two months later. The roots. They may present as mononeu- 2011, the patient presented with com- previously observed FDG-avid lesion ropathy, plexopathy, or generalized plaints of weakness and numbness in in the posterior compartment of the neuropathy. These neuropathies may the right foot. She was referred for PET- proximal right leg (tibial nerve lym- resemble an asymmetric mononeurop- CT study (Fig. 2a, b), which showed a phoma) showed marked interval de- athy multiplex, a generalized disorder fluorodeoxyglucose (FDG)-avid le- crease in metabolic activity (current such as chronic inflammatory demy- sion in the posterior compartment SUVmax, 3.8; previous SUVmax, 18.5). elinating polyradiculoneuropathy, or of the proximal right leg (maximum The PET-CT findings suggested a pos- even Guillain-Barré syndrome (5, 6). A standardized uptake value [SUVmax], itive response to chemotherapy. The literature review indicated a paucity of 18.4), with suspected lymphomatous previously observed focal FDG activ- previous reports regarding peripheral

a b c

d e f

Figure 1. a–f. Axial T2 (a), axial STIR (b), axial postcontrast T1-weighted fat-saturated (c), coronal T2-weighted (d), and coronal postcontrast T1-weighted fat-saturated (e) images demonstrated an elongated oval-shaped mass along the course of the ulnar nerve, located eccentrically to the nerve. The lesion showed predominantly peripheral enhancement on postcontrast images (c, e). High-power view (f) showed sheets of large lymphoid cells with irregular vesicular nuclei and prominent nucleoli (hematoxylin-eosin, ×400).

26 • January–February 2013 • Diagnostic and Interventional Radiology Agrawal et al. a b multiplanar capability can accurate- ly identify a mass involving a nerve. Demonstration of the relationship with the mass is important to exclude the possibility of other soft-tissue tumors. Tumor dimensions as well as the extent and relationship of the tumor with surrounding structures are accu- rately depicted, providing invaluable information to the surgeon in cases where surgery is planned (12). How- ever, despite its high sensitivity and excellent anatomical depiction, MRI lacks specificity. The MRI features of a peripheral nerve lymphoma can be mimicked by those of a neurogenic tumor (1). In our case, the mass was typ- ically eccentric in location, mimicking a nerve sheath tumor. Its T1-weighted, T2-weighted, and STIR signal inten- sities were also similar to those of a neurogenic tumor. The postcontrast images showed predominantly peripheral enhancement. Most solid neurogenic tumors have bright postcontrast c enhancement; however, peripheral enhancement could be observed in a cystic schwannoma. Thus, a peripheral nerve lymphoma should always be considered in the differential diagnosis of peripheral nerve tumor together with the much more common neurogenic tumors. The postresection specimen indicated that the mass was neither cystic nor necrotic; therefore, the discussion also encourages a more Figure 2. a–c. PET of whole body (a) and coronal PET-CT of lower limb (b) images demonstrated detailed study to determine if most peripheral nerve lymphomas or any an FDG-avid lesion in the in the posterior compartment of the proximal right leg (SUVmax, 18.4), suggestive of lymphomatous involvement. PET of whole body (a) and axial PET-CT (c) images particular cell type have predominant also showed a focal FDG-avid area in the posterior medial aspect of the right elbow (SUVmax, peripheral enhancement. 13.4), suggestive of either a postoperative change or residual tumor following surgery. PET-CT plays an important role in the follow-up of these patients on therapy (3). This method can determine nervous system lymphoma, and there tral nervous systems (1, 4, 8, 9). The the response to treatment by a decrease have been very few reported cases of B-cell type of non-Hodgkin lymphoma in activity and lesion size. PET-CT can solitary peripheral nerve lymphoma is the predominant type involving the also determine recurrence, and in cas- peripheral nerves, with the NK/T-cell presenting as a fusiform mass (1, 3, 4). es of known systemic lymphomas can Most of the peripheral nerve lympho- subtype being extremely rare (2, 4, 8). diagnose development of new mass- mas described in the literature have Our case was an NK/T-cell subtype of es. The fusion of PET and CT has the involved the sciatic nerve (4). Only lymphoma. The response of these lym- advantage of a higher confidence lev- one case of lymphoma involving the phomas to treatment is variable (10). el of lesion localization; therefore, an ulnar nerve has been reported in the Various treatment approaches have FDG-avid lesion may be determined to English literature (7). The natural his- been applied, including chemothera- be arising from a peripheral nerve. tory of these lymphomas is variable. py, radiotherapy, and surgery, alone In conclusion, we reported a rare case Most of the reported cases of primary and in various combinations (11). Pro- of an extranodal lymphoma present- peripheral nerve lymphomas have her- phylactic and therapeutic intrathecal ing as a peripheral nerve tumor. MRI is alded the onset of systemic lympho- methotrexate therapy is also common- helpful in lesion localization and surgi- ma, whereas there have been few cases ly used because these patients have an cal planning. MRI features may mimic found in patients with known system- increased risk of central nervous sys- a neurogenic tumor; therefore, periph- ic disease. In either case, it may be a tem relapse (1, 4, 8, 9). eral nerve lymphoma should be in- harbinger of a more disseminated dis- MRI plays an important role in the cluded in the differential diagnosis of ease involving the peripheral and cen- diagnosis. The high tissue contrast and a peripheral nerve tumor, particularly

Volume 19 • Issue 1 MRI and PET-CT for the lymphoma with peripheral nerve involvement • 27 References a b 1. Roncaroli F, Poppi M, Riccioni L, Frank F. Primary non-Hodgkin’s lymphoma of the sciatic nerve followed by localization in the central nervous system: case report and review of the literature. Neurosurgery 1997; 40:618–621. [CrossRef] 2. Kanamori M, Matsui H, Yudoh K. Soli- tary T-cell lymphoma of the sciatic nerve: case report. Neurosurgery 1995; 36:1203– 1205. [CrossRef] 3. Trojan A, Jermann M, Taverna C, Hany TF. Fusion PET-CT imaging of neurolymphomatosis. Ann Oncol 2002; 13:802– 805. [CrossRef] 4. Gonzalvo A, McKenzie C, Harris M, Biggs M. Primary non-Hodgkin’s lymphoma of the radial nerve: case report. Neurosur- gery 2010; 67:872–873. [CrossRef] 5. Kelly JJ, Karcher DS. Lymphoma and peripheral neuropathy: a clinical review. Mus- cle Nerve 2005; 31:301–313. [CrossRef] 6. Re D, Schwenk A, Hegener P, Bam- borschke S, Diehl V, Tesch H. Guil- lain Barré syndrome in a patient with non-Hodgkin’s lymphoma. Ann Oncol 2000; 11:217–220. [CrossRef] c 7. Choi AL, Koh SH, Jun SY, et al. Lym- phoma involving the ulnar nerve: sono- graphic findings. J Ultrasound Med 2008; 27:1527–1531. 8. Misdraji J, Ino Y, Louis DN, Rosenberg AE, Chiocca EA, Harris NL. Primary lymphoma of peripheral nerve: report of four cases. Am J Surg Pathol 2000; 24:1257–1265. [CrossRef] 9. Quinones-Hinojosa A, Friedlander RM, Boyer PJ, Batchelor TT, Chiocca EA. Solitary sciatic nerve lymphoma as an initial man- ifestation of diffuse neurolymphomatosis. Figure 3. a–c. Follow-up PET-CT study after chemotherapy. PET of whole body (a), sagittal PET- Case report and review of the literature. J CT of lower limbs (b), and axial PET-CT (c) images demonstrated a marked interval decrease in Neurosurg 2000; 92:165–169. [CrossRef] FDG activity in the previously seen FDG-avid lesions in the posterior compartment (a, b) of the 10. Descamps MJ, Barrett L, Groves M, et al. Prima- proximal right leg (current SUVmax, 3.8; previous SUVmax, 18.5) and in the posterior medial aspect ry sciatic nerve lymphoma: a case report and (a, c) of the right elbow (current SUVmax, 2.4; previous SUVmax, 13.4), suggesting a positive review of the literature. J Neurol Neurosurg response to chemotherapy. Psychiatry 2006; 77:1087–1089. [CrossRef] 11. Baehring JM, Damek D, Martin EC, Betensky RA, Hochberg FH. Neurolymphomatosis. in the setting of an already established peutic implications without the risk of Neuro Oncol 2003; 5:104–115. [CrossRef] lymphoma. PET-CT represents a novel invasive procedures. 12. Pillay PK, Hardy RW Jr, Wilbourn AJ, Tubbs RR. Solitary primary lymphoma of tool for imaging in relapse of peripher- Conflict of interest disclosure the sciatic nerve: case report. Neurosur- al nerve lymphoma and prompt thera- The authors declared no conflicts of interest. gery 1988; 23:370–371. [CrossRef]

28 • January–February 2013 • Diagnostic and Interventional Radiology Agrawal et al.